National Center for Emerging and Zoonotic Infectious Diseases
The Arboviruses Next Door: Orphaned and Emerging Arboviruses of the US
Holly R Hughes, Ph.D.Research Microbiologist
APHL annual meeting
June 3, 2018
Orphaned arbovirusesOrphan ≠ neglected
Orthobunyavirus (Order Bunyavirales, Family Peribunyaviridae)
Negative sense, single-stranded, segmented, RNA genome– Large (L) : RNA-dependent RNA
polymerase– Medium (M) : structural
polyprotein Gn-NSm-Gc– Small (S): nucleocapsid and NSs
20 serogroups– California (US/North America)– Bunyamwera (US/North America,
South America, Africa)
Guu et al. Bunyavirus: structure and replication. In Advances in Experimental Medicine and Biology. 2012
Segment reassortment (rapid evolution)
Superinfection of closely related viruses• Mosquitoes
Increased pathogenesis• Ngari (Garissa) virus• Schmallenberg virus
Vector/host expansion New ecological niches Prevalent in bunyavirusesVijaykrishna, D et al. PLoS Pathog. 2015 Jul; 11(7): e1004902
California serogroup Endemic viruses of public health importance
– La Crosse virus – pediatric encephalitis– Jamestown canyon virus– Snowshoe hare virus– California encephalitis virus
Human infection– Encephalitis– Febrile illness– Asymptomatic
Mosquito borne– “strict” vector and small mammalian vertebrate host preferences
Widely distributed
La Crosse virus
Aedes triseriatus (treeholemosquito)• Aggressive daytime-biting
Vertebrate hosts• Chipmunks and squirrels
Human infection• Fever (low viremia), headache,
nausea• Severe neuroinvasive disease
La Crosse virus
Changing distribution• Historically upper Midwest, now
central Atlantic• Widespread Midwest – Southeast
Clinical Lab Diagnosis• Difficult to culture and identify
with molecular methods• Serological diagnosis remains
primary method
La Crosse disease 2007-2016 (ArboNet)(~70 per year)
La Crosse virus
Changing distribution
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 16, No. 5, May 2010
Kraemer et.al. eLIFE 2015: 4; e08347
Predicted occurrence of Ae. albopictus
Jamestown Canyon virus
California serogroup Aedes and Ochlerotatus
• 26 species of mosquito • 3 tabanid (horse) flies
Vertebrate host• White-tailed deer (likely)• Wild ungulates and
domestic livestock
Human infection• Febrile, headache, nausea,
photophobia• Respiratory symptoms
• Not often reported• Meningitis and encephalitis
Predominantly in adults
Jamestown Canyon virus
Widely distributed• US and Canada• Likely under-reported
• 15 reported in 2016
Clinical Lab diagnosis• No human isolations to date
• RT-PCR of S segment• Serological diagnosis
primary method• Persistent IgM possible
Jamestown Canyon 2000-2013 (31 cases)Pastula et al. Am. J. Trop. Med. Hyg., 93(2), 2015, pp. 384–389
11 cases (2015), 15 (2016)
Cache Valley virus
Bunyamwera serogroup Anopheles
• >30 mosquito species
Vertebrate host• White-tailed deer
Widely distributed • North and Central America
Livestock disease• Abortion and still birth
Human infection• Neuroinvasive encephalitis• 5 human cases identified in US
(2015 most recent)• 18% seropositive in Yucatan
• Febrile illness
Clinical Lab diagnosis• PRNT primary method• Virus isolated from CSF and serum
• Real-time RT-PCR
Colorado tick fever (CTF) Reoviridae, genus Coltivirus Non-enveloped virion 12 segments Double-stranded RNA Tropism for hematopoietic stem cells
– Mature erythrocytes Virus found in RBCs ~ 6 weeks after
symptom onset
Colorado tick fever (CTF)
Dermacentor andersoni(Rocky Mountain wood tick)
Vertebrate hosts• Chipmunks, squirrels, and mice
Human infection• Febrile, head and body aches• Biphasic fever• Leukopenia• Rarely neuroinvasive
Colorado tick fever (CTF)
Distributed widely in Western States (4,000-10,000 feet)
Clinical lab diagnosis• Real-time RT-PCR
• Sensitive <21 dpo• RNA detected up to 42 dpo
• Delayed antibody response• PRNT• >15 dpo
Distribution of D. andersoni and CTF cases 2002-2012 (83)
www.cdc.gov/coloradotickfever
Emerging arboviruses
Heartland virus Order Bunyavirales, Family
Phenuiviridae, genus Phlebovirus– Ukuniemi serogroup
3 segment, negative sense RNA genome– Ambisense S segment
2009, Missouri Genetically similar to Severe Fever
with Thrombocytopenia Syndrome virus (SFTS)– 2009 China
Heartland virus
Tick associated disease Amblyomma americanum
(Lone star)• Virus isolation• Laboratory transmission
Vertebrate host unknown• Seropositive: white-tailed
deer, raccoon, coyote, moose
Riemersma and Komar 2015 EID
Heartland virus
Human infection• Febrile, headache, nausea,
muscle or joint pain, leukopenia, and thrombocytopenia
• Often confused with ehrlichiosis
Clinical lab diagnosis• Real-time RT-PCR• Serology
Heartland virus cases as of July 2017 (30)
www.cdc.gov
Bourbon virus
Orthomyxoviridae, genus Thogotovirus
6 segments, negative stranded RNA genome
Thogoto and Dhori viruses known human pathogens• Europe, Asia, Africa• Tick transmission
Kansas 2014Kosoy et.al. 2015 EID
Bourbon virus Tick associated Amblyoma americanum (Lone star)
• Isolated in ticks from MO 2013 and KS 2015
• Nymph and adult Human infection
• Febrile, thrombocytopenia, leukopenia
Clinical lab diagnosis• Real-time RT-PCR• PRNT
Distribution of A. americanum
www.cdc.gov
Yellow fever virus Flavivirus
• Positive RNA genome Aedes aegypti
• urban transmission
Haemagogus and Sabethes• sylvatic transmission (most common)
Human infection• Febrile ILI with jaundice• 12-15% severe disease• High fever, bleeding, shock, organ
failure
www.who.int/emergenices/yellow-fever
Clinical lab diagnosis• Serology• Real-time RT-PCR
Risk areas (vaccine recommended)
cdc.gov/yellowfever
Yellow fever virus
Recent notable outbreaks• 2016 Angola, Democratic
Republic of the Congo (3,137 suspect)
• 2016/2017 Brazil (777 confirmed)
• 2017 Nigeria (341 suspect)• 2018 Brazil (920 confirmed)
• 11 international travelers
For more information, contact CDC1-800-CDC-INFO (232-4636)TTY: 1-888-232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Thank you
Holly Hughes [email protected]